Medical devices

ABSTRACT

Medical devices, and related components and methods, are disclosed.

RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.11/458,171, filed Jul. 18, 2006, the entire disclosure of which isincorporated herein by reference.

TECHNICAL FIELD

This invention relates to medical devices, and to related components andmethods.

BACKGROUND

Therapeutic vascular occlusions (embolizations) are used to prevent ortreat pathological conditions in situ. Compositions including embolicparticles are used for occluding vessels in a variety of medicalapplications. Embolic particles can be delivered to a target site in abody of a subject using, for example, a catheter.

SUMMARY

In one aspect, the invention features a method that includes deliveringa catheter into a lumen of a subject. The catheter includes a generallytubular member having a lumen, a proximal region, and a distal region,and an inflatable member carried by a portion of the generally tubularmember. The method also includes curving the portion of the generallytubular member that carries the inflatable member within the lumen ofthe subject, and disposing at least one embolic material into the lumenof the generally tubular member.

In another aspect, the invention features a method that includesdelivering a catheter into a lumen of a subject. The catheter includes agenerally tubular member having a lumen, a proximal region, and a distalregion, and an inflatable member carried by a portion of the generallytubular member. The method also includes curving the portion of thegenerally tubular member that carries the inflatable member within thelumen of the subject, and flowing at least one contrast agent into thelumen of the generally tubular member.

In an additional aspect, the invention features a method of resectingliver tissue of a subject. The method includes delivering a catheterinto a lumen of a subject. The catheter includes a generally tubularmember having a lumen, a proximal region, and a distal region, and aninflatable member that is carried by a portion of the generally tubularmember. The method also includes inflating the inflatable member withinthe lumen of the subject, curving the portion of the generally tubularmember that carries the inflatable member within the lumen of thesubject, disposing embolic particles into the lumen of the generallytubular member, delivering the embolic particles into the lumen of thesubject, and resecting liver tissue of the subject.

Embodiments can also include one or more of the following.

The embolic material can include one or more embolic gels, embolicparticles, and/or embolic coils. The embolic particles can have anarithmetic mean diameter of about 3,000 microns or less and/or about onemicron or more.

The method can include disposing at least one embolic material into thelumen of the generally tubular member, and/or delivering at least oneembolic material into the lumen of the subject. The method can includerotating the portion of the generally tubular member that carries theinflatable member within the lumen of the subject. During and/or afterrotation of the portion of the generally tubular member, at least oneembolic material can be disposed into the lumen of the generally tubularmember, and/or at least one contrast agent can be flowed through thelumen of the generally tubular member. The method can include viewingthe embolic material (e.g., within the lumen of the subject) using X-rayfluoroscopy. The method can include resecting liver tissue of thesubject.

Curving the portion of the generally tubular member that carries theinflatable member can include removing an inner member from the lumen ofthe generally tubular member, and/or disposing an inner member into thelumen of the generally tubular member. The inner member can include aneedle, a guidewire, a stylet, or a combination thereof. Curving theportion of the generally tubular member that carries the inflatablemember can include inflating the inflatable member and/or aligning theportion of the generally tubular member with a longitudinal axis of thelumen of the subject.

The method can include inflating the inflatable member. The method caninclude delivering at least one embolic material and/or contrast agentinto the lumen of the generally tubular member during and/or afterinflation of the inflatable member. When inflated, the inflatable membercan have a diameter of at least about one centimeter (e.g., at leastabout two centimeters, at least about three centimeters) and/or at mostabout four centimeters (e.g., at most about three centimeters, at mostabout two centimeters). The inflatable member can have a wall includingat least two regions with different thicknesses. The inflatable membercan be eccentrically disposed on the portion of the generally tubularmember that carries the inflatable member.

The distal region of the generally tubular member can include a distalend of the generally tubular member, and the lumen of the generallytubular member can extend through the distal end of the generallytubular member.

The lumen of the subject can be a branch of a portal vein. The lumen ofthe subject can have a longitudinal axis. Delivering the catheter intothe lumen of the subject can include inserting the catheter into thelumen of the subject along an axis that is perpendicular to thelongitudinal axis of the lumen of the subject. Delivering the catheterinto the lumen of the subject can include inserting the catheter througha location in the skin of the subject and through a location in thelumen of the subject. The location in the lumen of the subject can belocated at most about three millimeters (e.g., at most about twomillimeters, at most about one millimeter), and/or at least about 0.1millimeter (e.g., at least about 0.5 millimeter, at least about onemillimeter), from the location in the skin of the subject.

Embodiments can include one or more of the following advantages.

The method can be used to deliver one or more embolic materials,contrast agents, and/or therapeutic agents to a target site (e.g., alumen of a subject) effectively and efficiently. Curving the distalregion of the generally tubular member can allow the embolic materials,contrast agents, and/or therapeutic agents to be delivered into thetarget site relatively easily and/or in a relatively high volume.

The method can include embolizing one or more branches of a portal vein.The embolization of the branches of the portal vein can be executedrelatively efficiently and with a relatively low likelihood of harm tothe subject (e.g., with a relatively low likelihood of perforation ofthe walls of the branches). In some embodiments, one or more branches ofa portal vein of a subject can be embolized prior to a liver resectionprocedure. This can, for example, enable one or more segments of theliver of the subject to be resected with relatively little blood loss,and/or enable one or more non-resected segments of the liver of thesubject to experience a relatively high rate of growth.

The distance between the point at which the catheter enters the body ofa subject and the point at which the catheter enters a target site(e.g., a lumen of the subject, such as a branch of a portal vein) can berelatively short. As a result, the catheter can be delivered into atarget site without having to navigate a long distance within the bodyof the subject first. This can, for example, reduce procedure timeand/or result in a relatively low likelihood of injury to the subject.

The method can be used to provide a targeted area for embolization,therapeutic agent delivery, and/or contrast agent delivery. For example,in some embodiments, a catheter can be used to occlude a portion of alumen of a subject and to deliver one or more embolic 110 materials,therapeutic agents, and/or contrast agents into a specific region of thelumen of the subject that is defined by the occlusion.

The method can include occluding a lumen of a subject, such as a branchof a portal vein, without using X-ray fluoroscopy prior to or during theocclusion. In some embodiments, the method can include using ultrasoundto locate a lumen of a subject, such as a branch of a portal vein, andpercutaneously inserting a balloon catheter into the lumen afteridentifying its location.

The method can include inflating an eccentrically disposed balloon of aballoon catheter within a lumen of a subject, and the eccentricity ofthe balloon can cause the inflated balloon to be relatively unlikely toslip and/or become dislodged from its location within the lumen of thesubject.

Features and advantages are in the description, drawings, and claims.

DESCRIPTION OF DRAWINGS

FIG. 1 is an illustration of a liver of a subject.

FIG. 2A illustrates the delivery of an embodiment of a needle into alumen of a subject.

FIG. 2B illustrates the delivery of an embodiment of balloon catheterinto the lumen of the subject of FIG. 2A.

FIG. 2C illustrates the inflation of a balloon of the balloon catheterof FIG. 2B within the lumen of the subject.

FIG. 2D illustrates the delivery of embolic material through the ballooncatheter of FIG. 2C and into the lumen of the subject.

FIG. 3A is a cross-sectional view of an embodiment of a ballooncatheter.

FIG. 3B is a cross-sectional view of a component of the balloon catheterof FIG. 3A.

FIG. 4 illustrates the delivery of embolic material into a lumen of asubject.

FIG. 5A illustrates the delivery of embolic material through anembodiment of a balloon catheter and into a lumen of a subject.

FIG. 5B illustrates the partial deflation of a balloon of the ballooncatheter of FIG. 5A.

FIG. 5C illustrates the rotation of the partially deflated balloon ofthe balloon catheter of FIG. 5B within the lumen of the subject.

FIG. 5D illustrates the inflation of the balloon of the balloon catheterof FIG. 5C, and the delivery of embolic material through the ballooncatheter and into the lumen of the subject.

FIG. 5E is a cross-sectional view of the lumen of the subject of FIGS.5A-5D, after embolic material has been delivered into the lumen of thesubject.

DETAILED DESCRIPTION

FIG. 1 shows a liver 10 of a subject 12, as well as a portal vein 14, asuperior mesenteric vein 16, an inferior mesenteric vein 18, a splenicvein 20, and a gastric vein 22. Portal vein 14, which is formed by theunion of superior mesenteric vein 16 and splenic vein 20, drains bloodinto liver 10. Portal vein 14 has many different branches that extendinto, and provide blood to, different segments of liver 10.

In some embodiments, it may be desirable to embolize one or more of thebranches of portal vein 14. For example, in certain embodiments, priorto a procedure in which one or more segments of liver 10 are to beresected (e.g., because they are tumorous), one or more of the branchesof portal vein 14 can be embolized. This embolization of selectedbranches of portal vein 14 can be used to slow or stop blood flow tosegments of liver 10 that will be resected, and to redirect blood flowto segments of liver 10 that will not be resected. The redirection ofblood flow to segments of liver 10 that will not be resected caninitiate hypertrophy, or exaggerated growth, of those segments. Thehypertrophy can be used to develop healthy liver tissue prior toresection of unhealthy liver tissue.

FIGS. 2A-2D illustrate a procedure that can be used to embolize a branch24 of portal vein 14.

First, branch 24 is located using ultrasound. Then, as shown in FIG. 2A,a needle 26 (e.g., a diagnostic needle from an AccuStick™ IntroducerSystem from. Boston Scientific Corp.) is inserted through a layer 28formed of skin and/or tissue, and into branch 24. Branch 24 has alongitudinal axis L, and needle 26 is inserted into branch 24 at anangle α that is perpendicular to longitudinal axis L.

As shown in FIG. 2B, a balloon catheter 30 is then inserted over needle26 and into branch 24, also at an angle α that is perpendicular tolongitudinal axis L of branch 24. Balloon catheter 30 enters layer 28 ata location L1 and enters branch 24 at a location L2. Typically, thedistance D between location L1 and location L2 can be relatively short,such that balloon catheter 30 does not have to navigate a long and/ortortuous path to reach branch 24. In some embodiments, distance D can beat most about three millimeters (e.g., at most about two millimeters)and/or at least about one millimeter (e.g., at least about twomillimeters). The delivery of balloon catheter 30 into branch 24, and/orthe location of balloon catheter 30 within branch 24, can be confirmedusing, for example, ultrasound.

As shown in FIG. 2B, balloon catheter 30 includes a generally tubularmember 32 having a proximal and a distal region 36 including the distalend 37 of generally tubular member 32. Balloon catheter 30 also includesa balloon 38 that is disposed on distal region 36 of generally tubularmember 32. Generally tubular member 32 has a central lumen 40 thatallows generally tubular member 32 to be inserted over needle 26.Generally tubular member 32 also has an inflation lumen 42 including aproximal end 44 and a distal end 46. Distal end 46 forms an opening 48in generally tubular member 32, such that inflation lumen 42 is in fluidcommunication with balloon 38.

After balloon catheter 30 has been inserted into branch 24 of portalvein 14, needle 26 is removed from central lumen 40 of generally tubularmember 32. As shown in FIG. 2C, balloon 38 is inflated by flowinginflation fluid (e.g., a saline solution mixed with a radiopaquecontrast agent) through inflation lumen 42. The removal of needle 26from generally tubular member 32, and the inflation of balloon 28, causedistal region 36 of generally tubular member 32 to become curved so thatit is aligned with longitudinal axis L of branch 24. Appropriatealignment can be achieved by positioning a guidewire, followed bypositioning balloon 38 over the guidewire.

As shown in FIG. 2D, after balloon 38 has been inflated, embolicparticles 50 are added into central lumen 40 of generally tubular member32, and are delivered into branch 24 of portal vein 14. A sufficientvolume of embolic particles 50 can be delivered into branch 24 to resultin the embolization of branch 24. In some embodiments, embolic particles50 can be disposed within a carrier fluid to form a composition (e.g., asuspension), which can be delivered through generally tubular member 32.The carrier fluid can be, for example, a pharmaceutically acceptablecarrier, such as saline, contrast agent, therapeutic agent, or acombination of these carriers. In certain embodiments, the carrier fluidcan include deionized water, water for injection, liquid polymer, gelpolymer, gas, or a combination of these carriers. In certainembodiments, embolic particles 50 may not be suspended in a carrierfluid. For example, embolic particles 50 alone can be delivered throughgenerally tubular member 32 and into branch 24.

Typically, the size of embolic particles 50 can be selected to providesufficient embolization of a lumen of a subject, such as branch 24 ofportal vein 14.

In some embodiments, one or more of embolic particles 50 can have amaximum dimension (e.g., a diameter) of about 3,000 microns or less(e.g., about 2,500 microns or less; about 2,000 microns or less; about1,500 microns or less; about 1,200 microns or less; about 1,000 micronsor less; about 900 microns or less; about 700 microns or less; about 500microns or less; about 400 microns or less; about 300 microns or less;about 100 microns or less; about 50 microns or less; about 10 microns orless; about five microns or less) and/or about one micron or more (e.g.,about five microns or more; about 10 microns or more; about 50 micronsor more; about 100 microns or more; about 300 microns or more; about 400microns or more; about 500 microns or more; about 700 microns or more;about 900 microns or more; about 1,000 microns or more; about 1,200microns or more; about 1,500 microns or more; about 2,000 microns ormore; about 2,500 microns or more). For example, in certain embodiments,one or more of embolic particles 50 can have a maximum dimension (e.g.,a diameter) of from about five microns to about 1,200 microns.

In certain embodiments, embolic particles 50 can have an arithmetic meandiameter of about 3,000 microns or less (e.g., about 2,500 microns orless; about 2,000 microns or less; about 1,500 microns or less; about1,200 microns or less; about 1,000 microns or less; about 900 microns orless; about 700 microns or less; about 500 microns or less; about 400microns or less; about 300 microns or less; about 100 microns or less;about 50 microns or less; about 10 microns or less; about five micronsor less) and/or about one micron or more (e.g., about five microns ormore; about 10 microns or more; about 50 microns or more; about 100microns or more; about 300 microns or more; about 400 microns or more;about 500 microns or more; about 700 microns or more; about 900 micronsor more; about 1,000 microns or more; about 1,200 microns or more; about1,500 microns or more; about 2,000 microns or more; about 2,500 micronsor more). The arithmetic mean diameter of a group of particles can bedetermined using a Beckman Coulter RapidVUE Image Analyzer version 2.06(Beckman Coulter, Miami, Fla.). Briefly, the RapidVUE takes an image ofcontinuous-tone (gray-scale) form and converts it to a digital formthrough the process of sampling and quantization. The arithmetic meandiameter of a group of particles (e.g., in a composition) can bedetermined by dividing the sum of the diameters of all of the particlesin the group by the number of particles in the group.

Embolic particles 50 can be formed of any of a number of differentmaterials. In some embodiments, embolic particles 50 can be formed ofone or more polymers. Examples of polymers include polyvinyl alcohols,polyacrylic acids, polymethacrylic acids, poly vinyl sulfonates,carboxymethyl celluloses, hydroxyethyl celluloses, substitutedcelluloses, polyacrylamides, polyethylene glycols, polyamides,polyureas, polyurethanes, polyesters, polyethers, polystyrenes,polysaccharides (e.g., alginate), polylactic acids, polyethylenes,polymethylmethacrylates, polycaprolactones, polyglycolic acids,poly(lactic-co-glycolic) acids (e.g., poly(d-lactic-co-glycolic) acids)and copolymers or mixtures thereof. In some embodiments, embolicparticles 50 can be formed of one or more styrenic block copolymers,such as styrene-isobutylene-styrene block copolymer (SIBS).

Particles are described, for example, in Lanphere et al., U.S. PatentApplication Publication No. US 2004/0096662 A1, published on May 20,2004, and entitled “Embolization”, DiCarlo et al., U.S. patentapplication Ser. No. 11/111,511, filed on Apr. 21, 2005, and entitled“Particles”, Song et al., U.S. patent application Ser. No. 11/314,056,filed on Dec. 21, 2005, and entitled “Block Copolymer Particles”, Songet al., U.S. patent application Ser. No. 11/314,557, filed on Dec. 21,2005, and entitled “Block Copolymer Particles”, and Song, U.S. patentapplication Ser. No. 11/355,301, filed on Feb. 15, 2006, and entitled“Block Copolymer Particles”, all of which are incorporated herein byreference.

FIG. 3A shows an enlarged cross-sectional view of balloon catheter 30.As shown in FIG. 3A, balloon 38, which is eccentrically disposed ongenerally tubular member 32, has a diameter D1 when balloon 38 isinflated. In some embodiments, diameter D1 can be at least about fivemillimeters (e.g., at least about 10 millimeters, at least about 20millimeters, at least about 30 millimeters) and/or at most about 40millimeters (e.g., at most about 30 millimeters, at most about 20millimeters, at most about 10 millimeters). In certain embodiments,diameter D1 can be from about 25 millimeters to about 33 millimeters.

Balloon 38 can be formed using, for example, a molding process.Typically, balloon 38 can be formed of one or more polymers (e.g.,homopolymers, copolymers). Examples of polymers that can be used inballoon 38 include silicone, polyurethanes, polyesters (e.g.,polyethylene terephthalate (PET) polymers, polybutylene terephthalate(PBT) polymers), polyamides (e.g., nylons such as aliphatic nylonsand/or aromatic nylons), and polyethylenes. In some embodiments, balloon38 can be formed of one or more polyether block polyamide copolymers. Incertain embodiments, balloon 38 can be formed of latex. In someembodiments, balloon 38 can include a blend of polymers. Balloons (e.g.,balloon materials) are described, for example, in Chin et al., U.S.Patent Application Publication No. US 2002/0165523 A1, published on Nov.7, 2002, and entitled “Multilayer Medical Balloon”, Pierre et al., U.S.Patent Application Publication No. US 2004/0078052 A1, published on Apr.22, 2004, and entitled “Multilayer Medical Device”, Chin et al., U.S.Pat. No. 6,951,675, and Sahatjian et al., U.S. Pat. No. 5,306,246, eachof which is incorporated herein by reference.

FIG. 3B shows generally tubular member 32 in its straight form. As shownin FIG. 3B, when in its straight form, generally tubular member 32 has alength L2. In some embodiments (e.g., some embodiments in whichgenerally tubular member 32 is designed to travel a relatively shortdistance within a body of a subject before reaching a target site),length L2 can be relatively short. In certain embodiments, length L2 canbe at least about 10 centimeters (e.g., at least about 20 centimeters,at least about 30 centimeters) and/or at most about 40 centimeters(e.g., at most about 30 centimeters, at most about 20 centimeters). Insome embodiments, length L2 can be about 30 centimeters.

Before generally tubular member 32 is inserted over needle 26, distalregion 36 of generally tubular member 32 is curved. The insertion ofgenerally tubular member 32 over needle 26 causes distal region 36 totemporarily straighten. When needle 26 is subsequently removed fromgenerally tubular member 32, distal region 36 re-assumes its curvedform.

In certain embodiments, distal region 36 of generally tubular member 32can be formed of one or more shape memory materials. Examples of shapememory materials include shape memory polymers, such as shape memorypolyurethanes (available from Mitsubishi), polynorbornene (e.g.,Norsorex™, available from Mitsubishi), polymethylmethacrylate (PMMA),poly(vinyl chloride), polyethylene (e.g., crystalline polyethylene),polyisoprene (e.g., trans-polyisoprene), styrene-butadiene copolymer,rubbers, or photocrosslinkable polymers including azo-dye, zwitterionicand/or other photochromic materials (as described in Shape MemoryMaterials, Otsuka and Wayman, Cambridge University Press, 1998).Additional examples of shape memory polymers include shape memoryplastics available from MnemoScience GmbH Pauwelsstrasse 19, D-52074Aachen, Germany.

In some embodiments, when a balloon such as balloon 38, which iseccentrically disposed on generally tubular member 32, is inflated, theeccentricity of the balloon can help to cause the distal region of thegenerally tubular member to become curved. As the larger side of theeccentrically disposed balloon expands, the expansion can cause thedistal region of the generally tubular member to curve toward thesmaller side of the eccentrically disposed balloon.

In certain embodiments, multiple (e.g., two, three) balloon catheterscan be used together in an embolization procedure. For example, FIG. 4shows a branch 100 of a portal vein that is located beneath a layer 104of skin and/or tissue. Two balloon catheters 106 and 108 have beeninserted into branch 100, and are used to deliver embolic particles 110into branch 100. As shown, balloon catheter 106 includes a generallytubular member 112 having a central lumen 114 and an inflation lumen116, and also includes a balloon 118 that is in fluid communication withinflation lumen 116. Balloon 118 is inflated, and occludes a portion 120of branch 100. Balloon catheter 108 includes a generally tubular member121 having a central lumen 122 and an inflation lumen 124, and alsoincludes a balloon 126 that is in fluid communication with inflationlumen 124. Balloon 126 is inflated, and occludes another portion 128 ofbranch 100. Embolic particles 110 are disposed into central lumens 114and 122 of balloon catheters 106 and 108, and delivered into branch 100.The occlusion of portions 120 and 128 of branch 100 by balloons 118 and126 provides a targeted region of branch 100 for embolization by embolicparticles 110.

In some embodiments, a balloon catheter can be used to define a targetsite for resection. For example, FIG. 5A shows a branch 200 of a portalvein in a body of a subject that is located beneath a layer 202 of skinand/or tissue. A balloon catheter 204 including a generally tubularmember 206 having a central lumen 208 and an inflation lumen 210, and aballoon 212, has been inserted into branch 200. An embolic gel 214 isdisposed into central lumen 208 of generally tubular member 206, and isdelivered into branch 200. As shown in FIG. 5B, after embolic gel 214has been delivered into branch 200, balloon 212 is slightly deflated,and, as shown in FIG. 5C, balloon catheter 204 is rotated 180 degrees.Thereafter, and as shown in FIG. 5D, an embolic gel 216 is disposed intocentral lumen 208 of generally tubular member 206, and is delivered intobranch 200. Balloon catheter 204 is then removed from branch 200, which,as shown in FIG. 5E, includes a region 218 that is occluded by embolicgel 214, and a region 220 that is occluded by embolic gel 216. Embolicgels 214 and 216 can be formed of the same materials or of differentmaterials. In certain embodiments, embolic gel 214 and/or embolic gel216 can include one or more polymers. Embolic gels are described, forexample, in U.S. Patent Application Publication No. US 2006/0045900 A1,published on Mar. 2, 2006, and entitled “Embolization”, which isincorporated herein by reference.

In some embodiments, embolic gels 214 and 216 can include one or moreradiopaque materials, materials that are visible by magnetic resonanceimaging (MRI-visible materials), ferromagnetic materials, and/orcontrast agents (e.g., ultrasound contrast agents). These materials canallow embolic gels 214 and 216 to be viewed using, for example, X-rayfluoroscopy, MRI, and/or ultrasound. When viewed using these techniques,embolic gels 214 and 216 can define a non-occluded region 222 betweenthem. In certain embodiments, a physician can use non-occluded region222 as a defined area in which resection can occur. Radiopaquematerials, MRI-visible materials, ferromagnetic materials, and contrastagents are described, for example, in Rioux et al., U.S. PatentApplication Publication No. US 2004/0101564 A1, published on May 27,2004, and entitled “Embolization”, which is incorporated herein byreference.

In some embodiments, a balloon catheter can be used in a procedure inwhich one or more therapeutic agents (e.g., a combination of therapeuticagents) are delivered into a target site in a body of a subject. Incertain embodiments, the therapeutic agents can be incorporated intoand/or onto embolic material that is delivered into the target siteusing the balloon catheter. In some embodiments, the therapeutic agentscan provide a medium in which embolic material is delivered to a targetsite using the balloon catheter. In certain embodiments, the therapeuticagents and/or can be delivered to the target site independently of anyembolic material.

Therapeutic agents include genetic therapeutic agents, non-genetictherapeutic agents, and cells, and can be negatively charged, positivelycharged, amphoteric, or neutral. Therapeutic agents can be, for example,materials that are biologically active to treat physiologicalconditions; pharmaceutically active compounds; proteins; gene therapies;nucleic acids with and without carrier vectors (e.g., recombinantnucleic acids, DNA (e.g., naked DNA), cDNA, RNA, genomic DNA, cDNA orRNA in a non-infectious vector or in a viral vector which may haveattached peptide targeting sequences, antisense nucleic acids (RNA,DNA)); oligonucleotides; gene/vector systems (e.g., anything that allowsfor the uptake and expression of nucleic acids); DNA chimeras (e.g., DNAchimeras which include gene sequences and encoding for ferry proteinssuch as membrane translocating sequences (“MTS”) and herpes simplexvirus-1 (“VP22”)); compacting agents (e.g., DNA compacting agents);viruses; polymers; hyaluronic acid; proteins (e.g., enzymes such asribozymes, asparaginase); immunologic species; nonsteroidalanti-inflammatory medications; oral contraceptives; progestins;gonadotrophin-releasing hormone agonists; chemotherapeutic agents; andradioactive species (e.g., radioisotopes, radioactive molecules, such asY90 particles). Non-limiting examples of therapeutic agents includeanti-thrombogenic agents; antioxidants; angiogenic and anti-angiogenicagents and factors; anti-proliferative agents (e.g., agents capable ofblocking smooth muscle cell proliferation, such as rapamycin); calciumentry blockers (e.g., verapamil, diltiazem, nifedipine); and survivalgenes which protect against cell death (e.g., anti-apoptotic Bcl-2family factors and Akt kinase).

Exemplary non-genetic therapeutic agents include: anti-thrombotic agentssuch as heparin, heparin derivatives, urokinase, and PPack(dextrophenylalanine proline arginine chloromethylketone);anti-inflammatory agents such as dexamethasone, prednisolone,corticosterone, budesonide, estrogen, acetyl salicylic acid,sulfasalazine and mesalamine;antineoplastic/antiproliferative/anti-mitotic agents such as paclitaxel,5-fluorouracil, cisplatin, methotrexate, doxorubicin, vinblastine,vincristine, epothilones, endostatin, angiostatin, angiopeptin,monoclonal antibodies capable of blocking smooth muscle cellproliferation, and thymidine kinase inhibitors; anesthetic agents suchas lidocaine, bupivacaine and ropivacaine; anti-coagulants such asD-Phe-Pro-Arg chloromethyl ketone, an RGD peptide-containing compound,heparin, hirudin, antithrombin compounds, platelet receptor antagonists,anti-thrombin antibodies, anti-platelet receptor antibodies, aspirin,prostaglandin inhibitors, platelet inhibitors and tick antiplateletfactors or peptides; vascular cell growth promoters such as growthfactors, transcriptional activators, and translational promoters;vascular cell growth inhibitors such as growth factor inhibitors (e.g.,PDGF inhibitor-Trapidil), growth factor receptor antagonists,transcriptional repressors, translational repressors, replicationinhibitors, inhibitory antibodies, antibodies directed against growthfactors, bifunctional molecules consisting of a growth factor and acytotoxin, bifunctional molecules consisting of an antibody and acytotoxin; protein kinase and tyrosine kinase inhibitors (e.g.,tyrphostins, genistein, quinoxalines); prostacyclin analogs;cholesterol-lowering agents; angiopoietins; antimicrobial agents such astriclosan, cephalosporins, aminoglycosides and nitrofurantoin; cytotoxicagents, cytostatic agents and cell proliferation affectors; vasodilatingagents; and agents that interfere with endogenous vasoactive mechanisms.

Exemplary genetic therapeutic agents include: anti-sense DNA and RNA;DNA coding for anti-sense RNA, tRNA or rRNA to replace defective ordeficient endogenous molecules, angiogenic factors including growthfactors such as acidic and basic fibroblast growth factors, vascularendothelial growth factor, epidermal growth factor, transforming growthfactor α and β, platelet-derived endothelial growth factor,platelet-derived growth factor, tumor necrosis factor a, hepatocytegrowth factor, and insulin like growth factor, cell cycle inhibitorsincluding CD inhibitors, thymidine kinase (“TK”) and other agents usefulfor interfering with cell proliferation, and the family of bonemorphogenic proteins (“BMP's”), including BMP2, BMP3, BMP4, BMP5, BMP6(Vgrl), BMP7 (OP1), BMP8, BMP9, BMP10, BM 11, BMP12, BMP13, BMP14,BMP15, and BMP16. Currently preferred BMP's are any of BMP2, BMP3, BMP4,BMP5, BMP6 and BMP7. These dimeric proteins can be provided ashomodimers, heterodimers, or combinations thereof, alone or togetherwith other molecules. Alternatively or additionally, molecules capableof inducing an upstream or downstream effect of a BMP can be provided.Such molecules include any of the “hedgehog” proteins, or the DNA'sencoding them. Vectors of interest for delivery of genetic therapeuticagents include: plasmids; viral vectors such as adenovirus (AV),adenoassociated virus (AAV) and lentivirus; and non-viral vectors suchas lipids, liposomes and cationic lipids.

Cells include cells of human origin (autologous or allogeneic),including stem cells, or from an animal source (xenogeneic), which canbe genetically engineered if desired to deliver proteins of interest.

Several of the above and numerous additional therapeutic agents aredisclosed in Kunz et al., U.S. Pat. No. 5,733,925, which is incorporatedherein by reference. Therapeutic agents disclosed in this patent includethe following:

“Cytostatic agents” (i.e., agents that prevent or delay cell division inproliferating cells, for example, by inhibiting replication of DNA or byinhibiting spindle fiber formation). Representative examples ofcytostatic agents include modified toxins, methotrexate, adriamycin,radionuclides (e.g., such as disclosed in Fritzberg et al., U.S. Pat.No. 4,897,255), protein kinase inhibitors, including staurosporin, aprotein kinase C inhibitor of the following formula:

as well as diindoloalkaloids having one of the following generalstructures:

as well as stimulators of the production or activation of TGF-beta,including Tamoxifen and derivatives of functional equivalents (e.g.,plasmin, heparin, compounds capable of reducing the level orinactivating the lipoprotein Lp(a) or the glycoproteinapolipoprotein(a)) thereof, TGF-beta or functional equivalents,derivatives or analogs thereof, suramin, nitric oxide releasingcompounds (e.g., nitroglycerin) or analogs or functional equivalentsthereof, paclitaxel or analogs thereof (e.g., taxotere), inhibitors ofspecific enzymes (such as the nuclear enzyme DNA topoisomerase II andDNA polymerase, RNA polymerase, adenyl guanyl cyclase), superoxidedismutase inhibitors, terminal deoxynucleotidyl-transferase, reversetranscriptase, antisense oligonucleotides that suppress smooth musclecell proliferation and the like. Other examples of “cytostatic agents”include peptidic or mimetic inhibitors (i.e., antagonists, agonists, orcompetitive or non-competitive inhibitors) of cellular factors that may(e.g., in the presence of extracellular matrix) trigger proliferation ofsmooth muscle cells or pericytes: e.g., cytokines (e.g., interleukinssuch as IL-1), growth factors (e.g., PDGF, TGF-alpha or -beta, tumornecrosis factor, smooth muscle- and endothelial-derived growth factors,i.e., endothelin, FGF), homing receptors (e.g., for platelets orleukocytes), and extracellular matrix receptors (e.g., integrins).Representative examples of useful therapeutic agents in this category ofcytostatic agents addressing smooth muscle proliferation include:subfragments of heparin, triazolopyrimidine (trapidil; a PDGFantagonist), lovastatin, and prostaglandins E1 or I2.

Agents that inhibit the intracellular increase in cell volume (i.e., thetissue volume occupied by a cell), such as cytoskeletal inhibitors ormetabolic inhibitors. Representative examples of cytoskeletal inhibitorsinclude colchicine, vinblastin, cytochalasins, paclitaxel and the like,which act on microtubule and microfilament networks within a cell.Representative examples of metabolic inhibitors include staurosporin,trichothecenes, and modified diphtheria and ricin toxins, Pseudomonasexotoxin and the like. Trichothecenes include simple trichothecenes(i.e., those that have only a central sesquiterpenoid structure) andmacrocyclic trichothecenes (i.e., those that have an additionalmacrocyclic ring), e.g., a verrucarins or roridins, including VerrucarinA, Verrucarin B, Verrucarin J (Satratoxin C), Roridin A, Roridin C,Roridin D, Roridin E (Satratoxin D), Roridin H.

Agents acting as an inhibitor that blocks cellular protein synthesisand/or secretion or organization of extracellular matrix (i.e., an“anti-matrix agent”). Representative examples of “anti-matrix agents”include inhibitors (i.e., agonists and antagonists and competitive andnon-competitive inhibitors) of matrix synthesis, secretion and assembly,organizational cross-linking (e.g., transglutaminases cross-linkingcollagen), and matrix remodeling (e.g., following wound healing). Arepresentative example of a useful therapeutic agent in this category ofanti-matrix agents is colchicine, an inhibitor of secretion ofextracellular matrix. Another example is tamoxifen for which evidenceexists regarding its capability to organize and/or stabilize as well asdiminish smooth muscle cell proliferation following angioplasty. Theorganization or stabilization may stem from the blockage of vascularsmooth muscle cell maturation in to a pathologically proliferating form.

Agents that are cytotoxic to cells, particularly cancer cells. Preferredagents are Roridin A, Pseudomonas exotoxin and the like or analogs orfunctional equivalents thereof. A plethora of such therapeutic agents,including radioisotopes and the like, have been identified and are knownin the art. In addition, protocols for the identification of cytotoxicmoieties are known and employed routinely in the art.

A number of the above therapeutic agents and several others have alsobeen identified as candidates for vascular treatment regimens, forexample, as agents targeting restenosis. Such agents include one or moreof the following: calcium-channel blockers, including benzothiazapines(e.g., diltiazem, clentiazem); dihydropyridines (e.g., nifedipine,amlodipine, nicardapine); phenylalkylamines (e.g., verapamil); serotoninpathway modulators, including 5-HT antagonists (e.g., ketanserin,naftidrofuryl) and 5-HT uptake inhibitors (e.g., fluoxetine); cyclicnucleotide pathway agents, including phosphodiesterase inhibitors (e.g.,cilostazole, dipyridamole), adenylate/guanylate cyclase stimulants(e.g., forskolin), and adenosine analogs; catecholamine modulators,including α-antagonists (e.g., prazosin, bunazosine), β-antagonists(e.g., propranolol), and α/β-antagonists (e.g., labetalol, carvedilol);endothelin receptor antagonists; nitric oxide donors/releasingmolecules, including organic nitrates/nitrites (e.g., nitroglycerin,isosorbide dinitrate, amyl nitrite), inorganic nitroso compounds (e.g.,sodium nitroprusside), sydnonimines (e.g., molsidomine, linsidomine),nonoates (e.g., diazenium diolates, NO adducts of alkanediamines),S-nitroso compounds, including low molecular weight compounds (e.g.,S-nitroso derivatives of captopril, glutathione and N-acetylpenicillamine) and high molecular weight compounds (e.g., S-nitrosoderivatives of proteins, peptides, oligosaccharides, polysaccharides,synthetic polymers/oligomers and natural polymers/oligomers),C-nitroso-, O-nitroso- and N-nitroso-compounds, and L-arginine; ACEinhibitors (e.g., cilazapril, fosinopril, enalapril); ATII-receptorantagonists (e.g., saralasin, losartin); platelet adhesion inhibitors(e.g., albumin, polyethylene oxide); platelet aggregation inhibitors,including aspirin and thienopyridine (ticlopidine, clopidogrel) and GPIIb/IIIa inhibitors (e.g., abciximab, epitifibatide, tirofiban,intergrilin); coagulation pathway modulators, including heparinoids(e.g., heparin, low molecular weight heparin, dextran sulfate,β-cyclodextrin tetradecasulfate), thrombin inhibitors (e.g., hirudin,hirulog, PPACK (D-phe-L-propyl-L-arg-chloromethylketone), argatroban),FXa inhibitors (e.g., antistatin, TAP (tick anticoagulant peptide)),vitamin K inhibitors (e.g., warfarin), and activated protein C;cyclooxygenase pathway inhibitors (e.g., aspirin, ibuprofen,flurbiprofen, indomethacin, sulfinpyrazone); natural and syntheticcorticosteroids (e.g., dexamethasone, prednisolone, methprednisolone,hydrocortisone); lipoxygenase pathway inhibitors (e.g.,nordihydroguairetic acid, caffeic acid; leukotriene receptorantagonists; antagonists of E- and P-selectins; inhibitors of VCAM-1 andICAM-1 interactions; prostaglandins and analogs thereof, includingprostaglandins such as PGE1 and PGI2; prostacyclins and prostacyclinanalogs (e.g., ciprostene, epoprostenol, carbacyclin, iloprost,beraprost); macrophage activation preventers (e.g., bisphosphonates);HMG-CoA reductase inhibitors (e.g., lovastatin, pravastatin,fluvastatin, simvastatin, cerivastatin); fish oils and omega-3-fattyacids; free-radical scavengers/antioxidants (e.g., probucol, vitamins Cand E, ebselen, retinoic acid (e.g., trans-retinoic acid), SOD mimics);agents affecting various growth factors including FGF pathway agents(e.g., bFGF antibodies, chimeric fusion proteins), PDGF receptorantagonists (e.g., trapidil), IGF pathway agents (e.g., somatostatinanalogs such as angiopeptin and ocreotide), TGF-β pathway agents such aspolyanionic agents (heparin, fucoidin), decorin, and TGF-β antibodies,EGF pathway agents (e.g., EGF antibodies, receptor antagonists, chimericfusion proteins), TNF-α pathway agents (e.g., thalidomide and analogsthereof), thromboxane A2 (TXA2) pathway modulators (e.g., sulotroban,vapiprost, dazoxiben, ridogrel), protein tyrosine kinase inhibitors(e.g., tyrphostin, genistein, and quinoxaline derivatives); MMP pathwayinhibitors (e.g., marimastat, ilomastat, metastat), and cell motilityinhibitors (e.g., cytochalasin B); antiproliferative/antineoplasticagents including antimetabolites such as purine analogs (e.g.,6-mercaptopurine), pyrimidine analogs (e.g., cytarabine and5-fluorouracil) and methotrexate, nitrogen mustards, alkyl sulfonates,ethylenimines, antibiotics (e.g., daunorubicin, doxorubicin, daunomycin,bleomycin, mitomycin, penicillins, cephalosporins, ciprofalxin,vancomycins, aminoglycosides, quinolones, polymyxins, erythromycins,tertacyclines, chloramphenicols, clindamycins, linomycins, sulfonamides,and their homologs, analogs, fragments, derivatives, and pharmaceuticalsalts), nitrosoureas (e.g., carmustine, lomustine) and cisplatin, agentsaffecting microtubule dynamics (e.g., vinblastine, vincristine,colchicine, paclitaxel, epothilone), caspase activators, proteasomeinhibitors, angiogenesis inhibitors (e.g., endostatin, angiostatin andsqualamine), and rapamycin, cerivastatin, flavopiridol and suramin;matrix deposition/organization pathway inhibitors (e.g., halofuginone orother quinazolinone derivatives, tranilast); endothelializationfacilitators (e.g., VEGF and RGD peptide); and blood rheology modulators(e.g., pentoxifylline).

Other examples of therapeutic agents include anti-tumor agents, such asdocetaxel, alkylating agents (e.g., mechlorethamine, chlorambucil,cyclophosphamide, melphalan, ifosfamide), plant alkaloids (e.g.,etoposide), inorganic ions (e.g., cisplatin), biological responsemodifiers (e.g., interferon), and hormones (e.g., tamoxifen, flutamide),as well as their homologs, analogs, fragments, derivatives, andpharmaceutical salts.

Additional examples of therapeutic agents include organic-solubletherapeutic agents, such as mithramycin, cyclosporine, and plicamycin.Further examples of therapeutic agents include pharmaceutically activecompounds, anti-sense genes, viral, liposomes and cationic polymers(e.g., selected based on the application), biologically active solutes(e.g., heparin), prostaglandins, prostcyclins, L-arginine, nitric oxide(NO) donors (e.g., lisidomine, molsidomine, NO-protein adducts,NO-polysaccharide adducts, polymeric or oligomeric NO adducts orchemical complexes), enoxaparin, Warafin sodium, dicumarol, interferons,interleukins, chymase inhibitors (e.g., Tranilast), ACE inhibitors(e.g., Enalapril), serotonin antagonists, 5-HT uptake inhibitors, andbeta blockers, and other antitumor and/or chemotherapy drugs, such asBiCNU, busulfan, carboplatinum, cisplatinum, cytoxan, DTIC, fludarabine,mitoxantrone, velban, VP-16, herceptin, leustatin, navelbine, rituxan,and taxotere.

Therapeutic agents are described, for example, in DiMatteo et al., U.S.Patent Application Publication No. US 2004/0076582 A1, published on Apr.22, 2004, and entitled “Agent Delivery Particle”, and in Schwarz et al.,U.S. Pat. No. 6,368,658, both of which are incorporated herein byreference.

While certain embodiments have been described, other embodiments arepossible.

As an example, in some embodiments, a catheter can include a generallytubular member having a distal region that is not formed of ashape-memory material and/or that is not curved prior to being deliveredinto a lumen of a subject. In some embodiments, the distal region of thegenerally tubular member can be formed of one or more polymers havingsufficient stiffness to allow the distal region to become curved. Forexample, in certain embodiments, the distal region can include one ormore polymers (e.g., polyurethanes, polyethylenes, polyvinylchlorides,polyamide polyether block copolymers) having a hardness of, for example,from 55 Shore D durometer to 72 Shore D durometer. The distal region canbecome curved (e.g., after the generally tubular member has beeninserted into a lumen of a subject) by inserting a device into the lumenof the generally tubular member, and manipulating the device within thelumen such that the device causes the distal region to become curved.

As another example, in certain embodiments, a catheter can include aballoon having a relatively thick portion and a relatively thin portion.For example, the catheter can include a balloon having one portion witha thickness of at most about 0.006 inch, and another portion with athickness of at least about 0.001 inch. When the balloon is inflated,the relatively thick portion of the balloon can experience less overallinflation than the relatively thin portion of the balloon. The greaterextent of inflation of the relatively thin portion of the balloon cancause the distal region of the generally tubular member to assume acurved shape. In some embodiments, a balloon having portions withdifferent thicknesses can be formed using a two-step molding process.First, a balloon mold (in the form of a mandrel) is oriented verticallyand dipped into a solution of a balloon material, to form a relativelyeven layer of balloon material over the mold. The layer of balloonmaterial is then allowed to dry, and thereafter the mold is rotated intoa horizontal position, and is only partially dipped into the balloonmaterial solution to form a second layer on a portion of the balloon.Once the balloon material has dried, the balloon can be removed from themold.

As an additional example, in certain embodiments, a catheter can includea balloon having different portions that are formed of differentmaterials. The result can be that the different portions of the ballooninflate at different rates when inflation fluid is added into theballoon. This differential inflation can cause the distal region of agenerally tubular member of the catheter to become curved.

As another example, while particles and gels have been described asexamples of embolic materials, in some embodiments, one or more otherdevices and/or materials can be used to embolize a target site. Forexample, in some embodiments, a mixture of N-butyl-2-cyanoacrylate(NBCA) ethiodized oil, and/or a mixture of fibrin glue with ethiodizedoil, can be used to embolize a lumen of a subject, such as a branch of aportal vein. In certain embodiments, one or more coils can be used in anembolization procedure. In some embodiments, a target site can beembolized using particles, and at the end of the embolization procedure,a relatively small number of coils can be added into the target site. Incertain embodiments, the coils can have enhanced visibility underultrasound relative to the particles, and can be used to determine thelocation of the embolized region under ultrasound. Coils are described,for example, in Elliott et al., U.S. patent application Ser. No.11/000,741, filed on Dec. 1, 2004, and entitled “Embolic Coils”, and inBuiser et al., U.S. patent application Ser. No. 11/311,617, filed onDec. 19, 2005, and entitled “Coils”, both of which are incorporatedherein by reference.

As a further example, while the delivery of embolic material using aballoon catheter has been described, in some embodiments, one or moreother types of materials can alternatively or additionally be deliveredinto a body of a subject using a balloon catheter. For example, incertain embodiments, one or more contrast agents, such as one or moreradiopaque and/or MM contrast agents, can be delivered into a body of asubject using a balloon catheter. Examples of radiopaque contrast agentsinclude Omnipaque™, Renocal®, iodiamide meglumine, diatrizoatemeglumine, ipodate calcium, ipodate sodium, iodamide sodium, iothalamatesodium, iopamidol, and metrizamide. Radiopaque contrast agents arecommercially available from, for example, Bracco Diagnostic. Examples ofMRI contrast agents include superparamagnetic iron oxides (e.g.,ferumoxides, ferucarbotran, ferumoxsil, ferumoxtran (e.g.,ferumoxtran-10), PEG-feron, ferucarbotran); gadopentetate dimeglumine;gadoterate meglumine; gadodiamide; gadoteridol; gadoversetamide;gadobutrol; gadobenate dimeglumine; mangafodipir trisodium; gadoxeticacid; gadobenate dimeglumine; macromolecular Gd-DOTA derivate;gadobenate dimeglumine; gadopentetate dimeglumine; ferric ammoniumcitrate; manganese chloride; manganese-loaded zeolite; ferristene;perfluoro-octylbromide; and barium sulfate. MM contrast agents aredescribed, for example, in Zhong et al., U.S. Patent ApplicationPublication No. US 2004/0186377 A1, published on Sep. 23, 2004, andentitled “Medical Devices”, which is incorporated herein by reference.In some embodiments, one or more therapeutic agents, such as one or moreof the therapeutic agents described above, can be delivered into thebody of a subject using a balloon catheter.

As another example, while the use of a balloon catheter and embolicmaterial in a portal vein embolization procedure has been described, insome embodiments, a balloon catheter and/or embolic material can be usedin one or more other procedures. For example, a balloon catheter and/orembolic material can be used in a procedure to treat one or more siteshaving cancerous lesions, such as the breast, prostate, lung, thyroid,or ovaries. A balloon catheter and/or embolic material can be used in,for example, neural, pulmonary, and/or AAA (abdominal aortic aneurysm)applications. A balloon catheter and/or embolic material can be used inthe treatment of, for example, fibroids, tumors, internal bleeding,arteriovenous malformations (AVMs), and/or hypervascular tumors. Aballoon catheter and/or embolic material can be used in, for example, aprocedure that is used to fill one or more aneurysm sacs, AAA sac (TypeII endoleaks), endoleak sealants, arterial sealants, and/or puncturesealants, and/or can be used to provide occlusion of other lumens suchas fallopian tubes. Fibroids can include uterine fibroids which growwithin the uterine wall (intramural type), on the outside of the uterus(subserosal type), inside the uterine cavity (submucosal type), betweenthe layers of broad ligament supporting the uterus (interligamentoustype), attached to another organ (parasitic type), or on a mushroom-likestalk (pedunculated type). Internal bleeding includes gastrointestinal,urinary, renal and varicose bleeding. AVMs are for example, abnormalcollections of blood vessels (e.g. in the brain) which shunt blood froma high pressure artery to a low pressure vein, resulting in hypoxia andmalnutrition of those regions from which the blood is diverted. Incertain embodiments, a balloon catheter and/or embolic material can beused to prophylactically treat a condition.

In some embodiments, a catheter including a balloon can be used in amitral valve repair procedure. For example, in certain embodiments, theballoon can be inflated and used to section off a portion of the mitralvalve that is to be treated. In some embodiments, a catheter including aballoon can be used to tighten a mitral valve. In certain embodiments, aballoon that is used in a mitral valve procedure can have a diameter ofat least about 0.5 inch and/or at most about 0.8 inch. In general, themitrial valve can be entered from below or from above. The distal end ofthe catheter can be manipulated to a target site where, for example, asuturing/stapling device can be passed through, and secure the tissue totighten the valve.

In certain embodiments, the arithmetic mean diameter of particles thatare delivered to a subject through a balloon catheter can vary dependingupon the particular condition to be treated. As an example, in certainembodiments in which the particles are used to embolize a liver tumor,the particles delivered to the subject can have an arithmetic meandiameter of about 500 microns or less (e.g., from about 100 microns toabout 300 microns; from about 300 microns to about 500 microns). Asanother example, in some embodiments in which the particles are used toembolize a uterine fibroid, the particles delivered to the subject canhave an arithmetic mean diameter of about 1,200 microns or less (e.g.,from about 500 microns to about 700 microns; from about 700 microns toabout 900 microns; from about 900 microns to about 1,200 microns). As anadditional example, in certain embodiments in which the particles areused to treat a neural condition (e.g., a brain tumor) and/or headtrauma (e.g., bleeding in the head), the particles delivered to thesubject can have an arithmetic mean diameter of less than about 100microns (e.g., less than about 50 microns). As a further example, insome embodiments in which the particles are used to treat a lungcondition, the particles delivered to the subject can have an arithmeticmean diameter of less than about 100 microns (e.g., less than about 50microns). As another example, in certain embodiments in which theparticles are used to treat thyroid cancer, the particles can have adiameter of about 1,200 microns or less (e.g., from about 1,000 micronsto about 1,200 microns).

As a further example, in some embodiments, particles having differentshapes, sizes, physical properties, and/or chemical properties, can beused together in an embolization procedure. The different particles canbe delivered into the body of a subject in a predetermined sequence orsimultaneously. In some embodiments, particles having different shapesand/or sizes can be capable of interacting synergistically (e.g., byengaging or interlocking) to form a well-packed occlusion, therebyenhancing embolization. Particles with different shapes, sizes, physicalproperties, and/or chemical properties, and methods of embolizationusing such particles are described, for example, in Bell et al., U.S.Patent Application Publication No. US 2004/0091543 A1, published on May13, 2004, and entitled “Embolic Compositions”, and in DiCarlo et al.,U.S. Patent Application Publication No. US 2005/0095428 A1, published onMay 5, 2005, and entitled “Embolic Compositions”, both of which areincorporated herein by reference.

As an additional example, while balloons having generally sphericalinflated shapes have been shown, in some embodiments, a balloon can havea non-spherical inflated shape. For example, in certain embodiments, aballoon can have a cylindrical or ellipsoidal inflated shape. The shapeof a balloon can be selected, for example, based on the shape of theregion the balloon is designed to treat.

As a further example, in certain embodiments, a catheter can include aballoon having multiple (e.g., two, three, four, five) layers. Balloonswith multiple layers are described, for example, in Chin et al., U.S.Patent Application Publication No. US 2002/0165523 A1, published on Nov.7, 2002, and entitled “Multilayer Medical Balloon”, Pierre et al., U.S.Patent Application Publication No. US 2004/0078052 A1, published on Apr.22, 2004, and entitled “Multilayer Medical Device”, and Chin et al.,U.S. Patent Application Publication No. US 2004/0146670 A1, published onJul. 29, 2004, and entitled “Multilayer Balloon Catheter”, each of whichis incorporated herein by reference.

As an additional example, while the use of a needle to temporarilystraighten the distal region of a generally tubular member of a ballooncatheter has been described, in some embodiments, one or more otherdevices can alternatively or additionally be used to temporarilystraighten the distal region of a generally tubular member. For example,in certain embodiments, a guidewire and/or a stylet can be used totemporarily straighten the distal region of a generally tubular member.

As a further example, in some embodiments, a balloon catheter can bedelivered into a target site (e.g., a lumen of a subject, such as aportal vein) through an introducer sheath.

As another example, in certain embodiments, a balloon catheter can bedelivered into a target site, and a microcatheter can then be deliveredinto a lumen of a generally tubular member of the balloon catheter.Thereafter, embolic material (e.g., embolic particles) can be deliveredinto the target site through the microcatheter.

As a further example, while a catheter including a generally tubularmember having two lumens has been described, in some embodiments, acatheter can include a generally tubular member having more than twolumens (e.g., three lumens, four lumens).

As another example, in some embodiments, a catheter can include agenerally tubular member having coaxial lumens. For example, a cathetercan include a generally tubular member having a central lumen and aninflation lumen that are coaxial.

As a further example, in certain embodiments, a lumen of a subject canhave a longitudinal axis, and a needle and/or a balloon catheter can beinserted into the lumen at an angle that is not perpendicular to thelongitudinal axis.

As an additional example, while embolic gels including one or moreradiopaque materials, MRI-visible materials, ferromagnetic materials,and/or contrast agents have been described, in some embodiments, embolicparticles and/or coils can include one or more of these materials.

Other embodiments are in the claims.

What is claimed is:
 1. A method for treating a target site in the body,the method comprising: inserting a catheter into a body lumen of apatient, the catheter comprising: a tubular member having a proximalportion, a distal portion and a lumen extending therein; and aninflatable member disposed on the distal portion of the tubular member;inflating the inflatable member such that at least a portion of thedistal portion of the tubular member substantially aligns with alongitudinal axis of the body lumen; delivering an embolic material intothe body lumen to form a first occlusion at a first location; deflatingthe inflatable member; rotating the tubular member within the body lumensuch that the embolic material may be injected in a second directiondifferent from the first direction.
 2. The method of claim 1, whereinthe inflatable member is eccentrically disposed on the distal portion ofthe tubular member.
 3. The method of claim 2, wherein the inflatablemember has a first wall portion having a first thickness and a secondwall portion having a second wall thickness, the second wall thicknessbeing greater than the first wall thickness.
 4. The method of claim 3,wherein the inflating the inflatable member includes inflating the firstwall portion at a greater rate than the second wall portion, and whereininflating the second wall portion at a greater rate forms a curve in thedistal portion of the tubular member.
 5. The method of claim 1, whereinthe embolic material is selected from the group consisting of embolicgels, embolic particles, embolic coils, and combinations thereof.
 6. Themethod of claim 1, wherein the embolic material comprises embolicparticles.
 7. The method of claim 1, wherein the embolic materialcomprises an embolic gel.
 8. The method of claim 1, wherein the bodylumen comprises one or more branches of the portal vein.
 9. The methodof claim 1, further comprising delivering embolic material at a secondlocation to form a second occlusion, and wherein the first occlusion isspaced away from the second occlusion.
 10. The method of claim 9,wherein the method further comprises resecting a liver tissue of apatient in a space between the first location and the second location.11. A method for occluding a body lumen, the method comprising:inserting an accessory device into a body lumen; delivering an embolicocclusion device over the accessory device, the embolic occlusion devicecomprising: a catheter including first and second lumens extendingtherein; and a balloon disposed along a distal portion of the catheter;expanding the balloon via the first catheter lumen such that at least aportion of the distal portion of the catheter rotates to a positionadjacent a first target site within the body lumen; delivering anembolic material into the body lumen through the second catheter lumento form a first occlusion at the first target site; deflating theballoon; rotating the embolic occlusion device such that the embolicmaterial may be injected to form a second occlusion at a second targetsite different from the first target site.
 12. The method of claim 11,wherein the balloon is eccentrically disposed on the distal portion ofthe catheter.
 13. The method of claim 12, wherein the balloon has afirst wall portion having a first thickness and a second wall portionhaving a second wall thickness, the second wall thickness being greaterthan the first wall thickness.
 14. The method of claim 13, wherein theinflating the balloon includes inflating the first wall portion at agreater rate than the second wall portion, and wherein inflating thesecond wall portion at a greater rate forms a curve in the distalportion of the catheter.
 15. The method of claim 11, wherein the embolicmaterial is selected from the group consisting of embolic gels, embolicparticles, embolic coils, and combinations thereof.
 16. The method ofclaim 11, wherein the embolic material comprises embolic particles. 17.The method of claim 11, wherein the embolic material comprises anembolic gel.
 18. The method of claim 11, wherein the body lumencomprises one or more branches of the portal vein.
 19. The method ofclaim 11, further comprising delivering embolic material at a secondlocation to form a second occlusion, and wherein the first occlusion isspaced away from the second occlusion.
 20. A medical device fordelivering embolic material, comprising: a tubular member having aproximal portion, a distal portion and a lumen extending therein; and aninflatable member disposed on the distal portion of the tubular member;wherein the inflatable member is configured to substantially align atleast a portion of the tubular member along a longitudinal axis of abody lumen; wherein the lumen of the tubular member is configured todeliver an embolic material into the body lumen to form a firstocclusion at a first location; wherein the tubular member is configuredto rotate within the body lumen such that the embolic material may beinjected in a second direction different from the first direction.